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Vaccine Therapy With PROSTVAC/TRICOM and Flutamide Versus Flutamide Alone to Treat Prostate Cancer

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ClinicalTrials.gov Identifier: NCT00450463
Recruitment Status : Completed
First Posted : March 22, 2007
Last Update Posted : December 7, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:


  • Flutamide is an approved drug for prostate cancer that blocks the effects of testosterone on prostate cancer cells and may slow the progression of the disease.
  • The vaccine in this study consists of a priming vaccine called PROSTVAC-V/TRICOM, made from vaccinia virus, and a boosting vaccine called PROSTVAC-F/TRICOM, made from fowlpox virus. DNA is inserted into the priming and boosting vaccine viruses to cause production of proteins that enhance immune activity and also to produce prostate specific antigen (PSA) a protein that is normally produced by the patient s tumor cells.
  • GM-CSF, given along with the vaccine, is a chemical that boosts the immune system. It is used in this study to try to increase the usefulness of the vaccine by increasing the number of immune cells at the vaccination site.


-To determine if treatment with a prostate cancer vaccine plus flutamide is more effective than flutamide alone in delaying disease progression in patients with prostate cancer.


  • Patients 18 years of age and older with androgen-insensitive prostate cancer that has not spread beyond the prostate gland.
  • Patients with a rising PSA who have already been treated with anti-iandrogen therapy (either bicalutamide or nilutamide).


  • There are two treatment groups in this study. Group A receives only flutamide; group B receive flutamide plus vaccine.
  • Patients in both groups receive flutamide by mouth three times a day.
  • Patients in group B receive PROSTVAC-V/TRICOM on day 1 and PROSTVAC-F/TRICOM on day 29 and again every 4 weeks. All vaccines are given as injections under the skin.
  • Patients have blood tests for PSA levels every month and scans every 3 months until the disease worsens.
  • After 3 months of therapy, patients receiving in group A (flutamide alone) may cross over to receive vaccine if they develop a rising PSA and scans show no sign of disease spread. Patients in group B (flutamide plus vaccine) stop flutamide and may continue vaccine therapy. At this point patients may continue to receive treatment until the disease progresses or PSA levels rise....

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Sargramostim (GM-CSF, Leukine) Drug: Flutamide (Eulexin) Biological: PROSTVAC-F/ TRICOM Biological: PROSTVAC-V/TRICOM Phase 2

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Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 53 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial Combining Vaccine Therapy With PROSTVAC/TRICOM and Flutamide vs. Flutamide Alone in Men With Androgen Insensitive, Non-Metastatic (D0.5) Prostate Cancer
Study Start Date : February 23, 2007
Primary Completion Date : April 27, 2017
Study Completion Date : June 8, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Active Comparator: A
Patients receive flutamide orally 3 times a day on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising PSA levels) without metastatic disease (as evidenced on scans), may receive vaccine treatment as defined in arm II beginning 4 weeks after flutamide therapy is discontinued.
Drug: Flutamide (Eulexin)
Orally administered, nonsteroidal, competitive antagonist of testosterone and other androgens at androgenic receptors and may alter the nuclear translocation of the androgen/receptor complex.
Experimental: B
Patients receive flutamide orally 3 times a day on days 1-28. Patients also receive recombinant vaccinia PSA vaccine subcutaneously (SC) on day 1 of course 1 only and recombinant fowlpox PSA vaccine SC on day 1 of all subsequent courses. Patients receive sargramostim (GM-CSF) SC on days 1-4. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising PSA levels), discontinue flutamide but may continue to receive vaccine treatment.
Drug: Sargramostim (GM-CSF, Leukine)
A recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) produced by recombinant DNA technology in yeast Saccharomyces cerevisiae). Sargramostim is a 127 amino acid glycoprotein, altered from the native, natural human GM-CSF molecule; the position 23 arginine has been replaced with a leucine to facilitate the expression of the protein in yeast.
Drug: Flutamide (Eulexin)
Orally administered, nonsteroidal, competitive antagonist of testosterone and other androgens at androgenic receptors and may alter the nuclear translocation of the androgen/receptor complex.
A recombinant fowlpox virus vector vaccine containing the genes for human PSA and three costimulatory molecules.
A recombinant vaccinia virus vector vaccine containing the genes for human PSA and three co-stimulatory molecules.

Outcome Measures

Primary Outcome Measures :
  1. Time to treatment failure [ Time Frame: 4-5 years ]

Secondary Outcome Measures :
  1. Time to development of metastatic disease
  2. Toxicity
  3. Response rate
  4. PSA and immune responses
  5. Immunologic effects

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 110 Years   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

A. Histopathological documentation of prostate cancer confirmed in the Laboratory of Pathology at the: NIH Clinical Center prior to starting this study. If no pathologic specimen is available, patients may enroll with a pathologist s report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.

B. Must have non-metastatic androgen insensitive prostate cancer with a rising PSA with castrate levels of testosterone and no evidence of metastatic disease on CT scan or bone scan. A rising PSA is defined as two consecutively rising PSA levels, separated by at least 1 month apart, with the last measurement that is greater than 1ng/ml. Patients on nilutamide therapy must undergo nilutamide withdrawal for at least 4 weeks and still show evidence of a rising PSA. Following treatment with bicalutamide, patients must undergo withdrawal for at least 6 weeks and still show evidence of a rising PSA.

C. Life expectancy greater than or equal to 6 months.

D. ECOG performance status of 0-1.

E. No systemic steroid or steroid eye drop use within 2 weeks prior to initiation of experimental therapy.

F. Hematological eligibility parameters:

  • Granulocyte count greater than or equal to 1,500/mm(3).
  • Platelet count greater than or equal to 100,000/mm(3)
  • Hgb greater than or equal to 9 Gm/dL
  • Lymphocyte count greater than or equal to 500/mm(3).

G. Biochemical eligibility parameters (within 16 days of starting therapy)

-Hepatic function: Bilirubin less than or equal to 1.5 mg/dl, OR patients with Gilbert's syndrome, a total bilirubin less than or equal to 3.0 mg/dL, AST and ALT less than 2.5 times upper limit of normal

H. No other active malignancies within the past 3 years (with the exception of non-melanoma skin cancers or carcinoma in situ of the bladder) or life threatening illnesses.

I. Willing to travel to the NIH for follow-up visits.

J. 18 years of age or greater.

K. Able to understand and sign informed consent.

L. Must agree to use effective birth control (such as a condom) or abstinence during and for a period of 4 months after the last vaccination therapy. Patients must be willing to remain on chemical castration therapy, unless they have had surgical castration.

M. Patients must have recovered from acute toxicities related to prior therapy or surgery.

N. Parameters for assessment of baseline renal function:

Serum creatinine less than or equal to 1.5 times the upper limit of normal OR creatinine clearance on a 24-h urine collection of greater than or equal to 60 mL/min.


A. Patients should have no evidence of being immunocompromised as listed below.

  • Human immunodeficiency virus positivity due to the potential for decreased tolerance and may be at risk for severe side effects.
  • Concurrent use of topical steroids (including steroid eye drops) or systemic steroids. Nasal or inhaled steroid use is permitted.
  • Patients who have undergone allogenic peripheral stem cell transplantation or solid organ transplantation requiring immunosuppression.

B. Patients who test positive for active Hepatitis B or Hepatitis C infection.

C. Patients should have no autoimmune diseases that have required treatment such as, Addison's disease, Hashimoto's thyroiditis, or systemic lupus erythematous, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome, active Grave's disease.

D. History of allergy or untoward reaction to prior vaccination with vaccinia virus or to any component of the vaccinia vaccine regimen.

E. Do not administer the recombinant vaccinia vaccine if the recipient, or for at least three weeks after vaccination, their close household contacts (close household contacts are those who share housing or have close physical contact) are: persons with active or a history of eczema or other eczematoid skin disorders; those with other acute, chronic or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds) until condition resolves; pregnant or nursing women; children 3 years of age and under; and immunodeficient or immunosuppressed persons (by disease or therapy), including HIV infection.

F. Serious intercurrent medical illness (e.g., one that requires treatment) which would interfere with the ability of the patient to carry out the treatment program, including, but not limited to, inflammatory bowel disease, Crohn's disease, ulcerative colitis, or active diverticulitis.

G. Patients with cardiac disease that have fatigue, palpitation, dyspnea or angina with ordinary physical activity (New York Heart Association class 2 or greater) are not eligible.

H. Patients with a history of congestive heart failure or who have objective evidence of congestive heart failure by physical exam or imaging are not eligible.

I. Patients with pulmonary disease that have fatigue or dyspnea with ordinary physical activity are not eligible.

J. Concurrent chemotherapy.

K. No known brain metastasis, or with a history of seizures, encephalitis, or multiple sclerosis.

L. Patients with a serious hypersensitivity reaction to egg products are not eligible.

M. Prior splenectomy.

N. Patients who have received prior flutamide therapy in the last year. (Patients treated with flutamide in the neoadjuvant or adjuvant setting or those previously treated with flutamide who did not have a rising PSA on treatment would be allowed to enroll on the protocol.)

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00450463

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
United States, New Jersey
Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08901
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Ravi A Madan, M.D. National Cancer Institute (NCI)
More Information

Additional Information:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00450463     History of Changes
Other Study ID Numbers: 070107
First Posted: March 22, 2007    Key Record Dates
Last Update Posted: December 7, 2017
Last Verified: June 7, 2017

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Hormonal Therapy
Combination Therapy
Prostate Specific Antigen
Prostate Cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Immunologic Factors
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Infective Agents
Antiprotozoal Agents
Antiparasitic Agents
Androgen Antagonists
Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents